Since 1981, the Division of Neuropathology has served as an informal brain bank. Over 220 brains from patients with sporadic and familial Alzheimer disease, a variety of other dementing illnesses and age-matched control subjects have been acquired. Tissues from these brains have been provided to three laboratories at our institution and sent to other institutions around the country. Forty-three publications !and presentations over the last three years have resulted from the studies of these tissues. However, no quantitative and detailed topographic assessment of the pathologic changes present in these brains have been carried out because of lack of funding and of basic clinical in formation on most of the subjects. In this Neuropathology Core, we now propose to establish a formal brain bank for a multidisciplinary study of a cohort of 200 clinically well characterized patients with dementia and 100 control subjects. Autopsies will be carried out with minimum post- mortem interval. The tissues obtained will be distributed to five research projects of this application and to other research projects funded by four different grants. The pathologic diagnosis will be established by the histologic examination of 21 tissue blocks comprising the entire frontal lobe at the level of Brodman area 44, the temporal lobe at the level of areas 41 and 42 and including the hippocampal formation, the parietal lobe including area 40 and 39, and the occipital lobe; central nuclei including thalamus, lenticular nucleus, caudate nucleus and insula, various levels of the brain stem, cerebellum and spinal cord will also be examined. Appropriate histological staining procedures and, if necessary, immunostaining will be used. The severity and topography of the lesions will be determined in random areas of the cerebral cortex from all lobes. These cortical areas will be analyzed to determine densities of neurons, neuritic plaques, neurofibrillary tangles as well as of cortical and meningeal vessels containing amyloid deposits. More extensive morphometric analyses will be carried out in anatomically better defined cortical areas in conjunction with the Image Analysis Core. The Neuropathology Core that we propose will provide not only well characterized tissues to the various projects of this application and to other research programs, but it will also generate information on the nature, severity and distribution of the lesions which will be needed to establish detailed correlations between pathologic changes and diverse functional deficits.